Title:
CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS
Document Type and Number:
WIPO Patent Application WO/2011/014973
Kind Code:
A3
Abstract:
Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of formulae Ia and Ib are constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. These macrocycles Ia and Ib are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being the agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), ion channels and signal transduction pathways. In particular, these macrocycles act as antagonists of the motilin receptor, the FP receptor and the purinergic receptors P2Y1, as modulators of the serotonin receptor of subtype 5-HT2B, as blockers of the voltage-gated potassium channel Kv1.3 and as inhibitors of the β-catenin-dependent "canonical" Wnt pathway. Thus they are showing great potential as medicaments for a variety of diseases.
Inventors:
OBRECHT DANIEL (CH)
ERMERT PHILIPP (DE)
OUMOUCH SAID (FR)
LACH FRANCK (FR)
LUTHER ANATOL (DE)
MARX KARSTEN (DE)
MOEHLE KERSTIN (DE)
ERMERT PHILIPP (DE)
OUMOUCH SAID (FR)
LACH FRANCK (FR)
LUTHER ANATOL (DE)
MARX KARSTEN (DE)
MOEHLE KERSTIN (DE)
Application Number:
PCT/CH2010/000191
Publication Date:
April 21, 2011
Filing Date:
August 03, 2010
Export Citation:
Assignee:
POLYPHOR AG (CH)
OBRECHT DANIEL (CH)
ERMERT PHILIPP (DE)
OUMOUCH SAID (FR)
LACH FRANCK (FR)
LUTHER ANATOL (DE)
MARX KARSTEN (DE)
MOEHLE KERSTIN (DE)
OBRECHT DANIEL (CH)
ERMERT PHILIPP (DE)
OUMOUCH SAID (FR)
LACH FRANCK (FR)
LUTHER ANATOL (DE)
MARX KARSTEN (DE)
MOEHLE KERSTIN (DE)
International Classes:
C07D498/04; A61K31/4745; A61K31/695; A61P1/06; A61P25/24; C07D497/18; C07D498/18; C07F7/08
Domestic Patent References:
| WO2001077113A2 | 2001-10-18 |
Foreign References:
| EP0807639A2 | 1997-11-19 |
Other References:
CHEN ET AL.: "Synthesis of Novel 4-tert-Alkyl Ether Proline-Based 16- and 17-Membered Macrocyclic Compounds", J. ORG. CHEM., vol. 67, 2002, pages 2730 - 2733, XP002580115
ARASAPPAN ET AL.: "Novel Dipeptide Macrocycles from 4-Oxo, -Thio, and -Amino-Substituted Proline Derivatives", J. ORG. CHEM., vol. 67, 2002, pages 3923 - 3926, XP002580116
CHEN ET AL.: "NOVEL POTENT HEPATITIS C VIRUS NS3 SERINE PROTEASE INHIBITORS DERIVED FROM PROLINE-BASED MACROCYCLES", J. MED. CHEM., vol. 49, 7 January 2006 (2006-01-07), pages 995 - 1005, XP002447441
MARSAULT ET AL.: "Discovery of a new class of macrocylic antagonists to the human motilin receptor", J. MED. CHEM., vol. 49, no. 24, 1 January 2006 (2006-01-01), pages 7190 - 7197, XP002484961
MARSAULT ET AL: "Potent macrocyclic antagonists to the motilin receptor presenting novel unnatural amino acids", BIOORG. MED. CHEM. LETT., vol. 17, no. 15, 1 August 2007 (2007-08-01), pages 4187 - 4190, XP022144671
ROBINSON ET AL.: "The design, structures and therapeutic potential of protein epitope mimetics", DRUG DISCOVERY TODAY, vol. 13, no. 21-22, 1 November 2008 (2008-11-01), pages 944 - 951, XP025574298
ARASAPPAN ET AL.: "Novel Dipeptide Macrocycles from 4-Oxo, -Thio, and -Amino-Substituted Proline Derivatives", J. ORG. CHEM., vol. 67, 2002, pages 3923 - 3926, XP002580116
CHEN ET AL.: "NOVEL POTENT HEPATITIS C VIRUS NS3 SERINE PROTEASE INHIBITORS DERIVED FROM PROLINE-BASED MACROCYCLES", J. MED. CHEM., vol. 49, 7 January 2006 (2006-01-07), pages 995 - 1005, XP002447441
MARSAULT ET AL.: "Discovery of a new class of macrocylic antagonists to the human motilin receptor", J. MED. CHEM., vol. 49, no. 24, 1 January 2006 (2006-01-01), pages 7190 - 7197, XP002484961
MARSAULT ET AL: "Potent macrocyclic antagonists to the motilin receptor presenting novel unnatural amino acids", BIOORG. MED. CHEM. LETT., vol. 17, no. 15, 1 August 2007 (2007-08-01), pages 4187 - 4190, XP022144671
ROBINSON ET AL.: "The design, structures and therapeutic potential of protein epitope mimetics", DRUG DISCOVERY TODAY, vol. 13, no. 21-22, 1 November 2008 (2008-11-01), pages 944 - 951, XP025574298
Attorney, Agent or Firm:
BRAUN, André (Reussstrasse 22, Basel, CH)
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